Primary congenital glaucoma: We are always on the way.

Primary congenital glaucoma (PCG), a developmental glaucoma occurring due to angle anomaly, earns growing concerns among ophthalmologists for its vision-damaging attribute. The incidence of PCG varies among races and geographic regions and is mostly genetically associated. Theories have been posed in attempt to address the etiology of this congenital maldevelopment and in the meanwhile providing evidence for feasibility of PCG surgeries. In regard to the clinical aspects of this entity, both the clinical characteristics and general principals of management are introduced, with angle surgeries highlighted for clarifying details including their success rates, key points for a successful surgical intervention, postoperative management, and follow-up strategies. Taking patients' vision-associated quality of life into consideration, we stressed that further perceptual learning and low vision rehabilitation are momentous. However, much has yet to be elucidated in respect of the truly comprehensive pathogenesis underneath as well as means by which clinical outcomes of PCG can be further improved. We are now looking forward to innovative therapeutic approaches like gene therapy in specific genes in the future, with the hope of improving their life-long visual quality in those young patients.

Profiling cells with DELs: Small molecule fingerprinting of cell surfaces.

DNA-encoded small molecule library technology has recently emerged as a new paradigm for identifying ligands against drug targets. To date, it has been used to identify ligands against targets that are soluble or overexpressed on cell surfaces. Here, we report applying cell-based selection methods to profile surfaces of mouse C2C12 myoblasts and myotube cells in an unbiased, target agnostic manner. A panel of on-DNA compounds were identified and confirmed for cell binding selectivity. We optimized the cell selection protocol and employed a novel data analysis method to identify cell selective ligands against a panel of human B and T lymphocytes. We discuss the generality of using this workflow for DNA encoded small molecule library selection and data analysis against different cell types, and the feasibility of applying this method to profile cell surfaces for biomarker and target identification.

Mesenchymal stem cells inhibit ferroptosis by activating the Nrf2 antioxidation pathway in severe acute pancreatitis-associated acute lung injury.

Severe acute pancreatitis-associated acute lung injury (SAP-ALI) remains a significant challenge for healthcare practitioners because of its high morbidity and mortality; therefore, there is an urgent need for an effective treatment. Mesenchymal stem cells (MSCs) have shown significant potential in the treatment of a variety of refractory diseases, including lung diseases. This study aimed to investigate the protective effects of MSCs against SAP-ALI and its underlying mechanisms. Our results suggest that MSCs mitigate pathological injury, hemorrhage, edema, inflammatory response in lung tissue, and lipopolysaccharide (LPS)-induced cell damage in RLE-6TN cells (a rat alveolar epithelial cell line). The results also showed that MSCs, similar to the effects of ferrostatin-1 (ferroptosis inhibitor), suppressed the ferroptosis response, which was manifested as down-regulated Fe2+, malondialdehyde, and reactive oxygen species (ROS) levels, and up-regulated glutathione peroxidase 4 (GPX4) and glutathione (GSH) levels in vivo and in vitro. The activation of ferroptosis by erastin (a ferroptosis agonist) reversed the protective effect of MSCs against SAP-ALI. Furthermore, MSCs activated the nuclear factor erythroid 2 associated factor 2 (Nrf2) transcription factor, and blocking the Nrf2 signaling pathway with ML385 abolished the inhibitory effect of MSCs on ferroptosis in vitro. Collectively, these results suggest that MSCs have therapeutic effects against SAP-ALI. The specific mechanism involves inhibition of ferroptosis by activating the Nrf2 transcription factor.

A new methodology to reveal potential nucleic acid modifications associated with the risk of endometrial cancer through dispersive solid-phase extraction coupled with UHPLC-QE-Orbitrap-MS/MS and HPLC-UV.

Nucleic acid modifications have attracted increasing attention in recent years since they have been found to be related to a number of diseases including cancer. Previous studies have shown that the early development of endometrial cancer (EC) is often accompanied by changes in methylation levels of related genes, and the expression of related proteins that regulate reactive oxygen species (ROS) shows significant differences in EC cells and tissues. However, it has not been reported whether nucleic acid modifications related to methylation or ROS can serve as biomarkers for EC. Accurate quantification of these nucleic acid modifications still has challenges because their amounts in urine are very low and the interferences in urine are complicated. In this study, a novel dispersive solid-phase extraction (DSPE) method based on chitosan-carbon nanotube-Al2O3 (CS-CNT-Al2O3) has been established for the analysis of 5-hydroxymethyluracil (5 mU), 5-methyl-2'-deoxycytidine (5-mdC), 5-hydroxymethyl-2'-deoxycytidine (5-hmdC), 5-formyl-2'-deoxycytidine (5-fdC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in EC patient urine samples coupled with UHPLC-QE-Orbitrap-MS/MS and HPLC-UV. Firstly, the synthesis of the CS-CNT-Al2O3 nanocomposite was conducted by a sono-coprecipitation method and was characterized by scanning electron microscope (SEM), energy dispersive spectrometer (EDS), and Fourier transform infrared (FTIR). Under the optimal extraction conditions of DSPE, we successfully quantified 5 mU, 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG in urine samples from 37 EC patients and 39 healthy controls. The results showed that there were significant differences in the levels of 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG in EC patients compared to the healthy control group. The receiver operator characteristic (ROC) curve analysis was carried out to evaluate the potential of 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG to distinguish EC patients from healthy volunteers. The area under the curve (AUC) for 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG was 0.7412, 0.667, 0.8438, and 0.7981, respectively. It indicated that 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG had certain potential in distinguishing between EC patients and healthy volunteers and they could act as potential non-invasive biomarkers for early diagnosis of EC. Moreover, the present study would stimulate investigations of the effects of nucleic acid modifications on the initiation and progression of EC.

Selective Upcycling of Polyethylene Terephthalate towards High-valued Oxygenated Chemical Methyl p-Methyl Benzoate using a Cu/ZrO2 Catalyst.

Upgrading of polyethylene terephthalate (PET) waste into valuable oxygenated molecules is a fascinating process, yet it remains challenging. Herein, we developed a two-step strategy involving methanolysis of PET to dimethyl terephthalate (DMT), followed by hydrogenation of DMT to produce the high-valued chemical methyl p-methyl benzoate (MMB) using a fixed-bed reactor and a Cu/ZrO2 catalyst. Interestingly, we discovered the phase structure of ZrO2 significantly regulates the selectivity of products. Cu supported on monoclinic ZrO2 (5 %Cu/m-ZrO2 ) exhibits an exceptional selectivity of 86 % for conversion of DMT to MMB, while Cu supported on tetragonal ZrO2 (5 %Cu/t-ZrO2 ) predominantly produces p-xylene (PX) with selectivity of 75 %. The superior selectivity of MMB over Cu/m-ZrO2 can be attributed to the weaker acid sites present on m-ZrO2 compared to t-ZrO2 . This weak acidity of m-ZrO2 leads to a moderate adsorption capability of MMB, and facilitating its desorption. Furthermore, DFT calculations reveal Cu/m-ZrO2 catalyst shows a higher effective energy barrier for cleavage of second C-O bond compared to Cu/t-ZrO2 catalyst; this distinction ensures the high selectivity of MMB. This catalyst not only presents an approach for upgrading of PET waste into fine chemicals but also offers a strategy for controlling the primary product in a multistep hydrogenation reaction.

Diffraction efficiency analysis of dual-layer diffractive elements with oblique incident angles.

This paper proposes a method that combines the effective area method and the oblique factors to analyze and design dual-layer diffractive optical elements at large incident angles. The method considers the effects of shadow and shield on the diffraction efficiency, as well as the correction of phase delay due to oblique incidence. The relationships among the diffraction efficiency, incident wavelengths, incident angles and period widths were analyzed with our method. A detailed comparison of the proposed method with the scalar diffraction theory is presented. The method was validated by numerical simulations of vector diffraction theory and showed similar diffraction efficiency distributions at different wavelengths and incident angles. The method provides a simple and efficient way to design and apply DLDOEs.

Urine levels of estrogen and its metabolites in premenopausal middle-aged women with different degrees of obesity and their correlation with glucose and lipid metabolism.

Objectives: To determine the levels of estrogen and estrogen metabolites in the urine of premenopausal women with obesity and their correlation with glucose and lipid metabolism. Methords: 135 premenopausal women were selected from the same area. According to the body mass index (BMI), they were divided into four different groups. High performance liquid chromatography-mass spectrometry (HPLC/MS) was adopted to detect the concentrations of estrogen and estrogen metabolites in the urine. The influencing factors of BMI were analyzed, the correlation between the urinary degrees of estrogen and estrogen metabolites and glucose and lipid metabolism levels was assessed. Results: (1) The concentrations of 17ß-estradiol (E2), estrone (E1), 16α-hydroxyestrone (16α-OHE1) and 2-hydroxyestrone (2-OHE1) gradually increased with increasing BMI (p < 0.05). (2) Stepwise regression analysis displayed that the concentrations of E2, 16α-OHE1 and 2-OHE1 in urine were significantly positively correlated with BMI (p < 0.05). (3) The concentrations of E2, E1, 16α-OHE1, 2-OHE1 and 16α-OHE1/2-OHE1 in urine were greatly positively related to fasting insulin (FIN), Triglyceride (TG), Total Cholesterol (TC) and Low-density lipoprotein (LDL) (p < 0.05). And they were greatly negatively related to High-density lipoprotein (HDL) (p < 0.05). Conclusions: Early screening can reflect the degree of obesity and glucose and lipid metabolism disorders in premenopausal middle-aged women, thereby providing guidance for improving the prognosis of obese women.

A strategy for quality evaluation of complex herbal preparations based on multi-color scale and efficacy-oriented high-performance thin-layer chromatography characteristic fingerprint combined with chemometric method: Sanwujiao Pills as an example.

To rapidly evaluate the quality of complex herbal preparations, a new strategy was proposed based on multi-color scale and efficacy-oriented high-performance thin-layer chromatography (HPTLC) characteristic fingerprint combined with chemometric method. Firstly, effective components were screened through high-performance liquid chromatography with ultraviolet detection and evaporative light-scattering (HPLC-UV-ELSD), using multi-wavelength fusion combined with network pharmacology and molecular docking techniques. Subsequently, guided by the effective components, the targeted HPTLC characteristic fingerprint was established by multi-color scale scanning. Finally, combined with the chemometric method, the consistency of the preparation quality was evaluated, the marker components leading to quality differences were screened, and the quality control limit was established. Sanwujiao Pills (SWJPs) is a herbal preparation composed of six herbs for treating rheumatoid arthritis (RA). Through this strategy, four HPTLC characteristic fingerprints were established, they were derived from five herbs and guided by eight effective components in SWJPs. Through similarity, clustering heatmap, principal component analysis (PCA), and orthogonal partial least squares discriminant analysis (OPLS-DA), the quality distinctions among the 12 batches of SWJPs were determined. These batches were categorized into two groups based on their production time, and eight components affecting the quality of the preparation were identified. Meanwhile, the quality control threshold for SWJPs was determined based on Hotelling's T2 and DModX methods. This strategy aims to rapidly evaluate the quality of complex herbal preparations by HPTLC and extends the application of HPTLC fingerprint chromatography for identifying herbal medicine species and activity-related quality detection. The proposed strategy is also helpful for the quality control of other complex herbal preparations.

Association of Urinary Levels of Estrogens and Estrogen Metabolites with the Occurrence and Development of Endometrial Hyperplasia Among Premenopausal Women.

Endometrial cancer is known to be an estrogen-dependent cancer, and it is believed that exposure to estrogens increases the risk of developing endometrial cancer in the absence of progesterone. Estrogens and estrogen metabolites may help to predict the risk of endometrial hyperplasia (EH) with atypia. Estrogens and estrogen metabolites were measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) in the first morning urine sample collected from 150 patients with EH and 50 healthy premenopausal women in the study. In healthy premenopausal women, the level of 16α-hydroxyestrone (16α-OHE1) in the overweight group was significantly higher than that in the lean group (p < 0.05). The levels of 4-hydroxyestradiol (4-OHE2) and 16α-OHE1 were elevated in the AEH group as compared to that in the control group (p < 0.05). Overweight is related to EH incidence as it causes an imbalance of estrogen metabolites. This study provides identifies potential biomarkers for estrogen-induced AEH.

Brightening up Full-Color and White Circularly Polarized Luminescence through Chiral Induction and Circularly Polarized Light Excitation.

Preparation of chiral materials from achiral helical polymers has aroused great interest among researchers. In this work, chiral small molecules were utilized to accomplish chiral induction toward racemic helical polyacetylene via intermolecular π-π stacking by which chiral films with strong optical activity were fabricated. Furthermore, introducing fluorescent components generated full-color and white circularly polarized luminescence (CPL). A CPL generation mechanism is proposed accordingly, namely circularly polarized light excitation (CP-Ex). CPL emission and amplification of the luminescence dissymmetry factor were achieved under the synergetic effect of CP-Ex and chirality transfer. The CP-Ex mechanism was further verified by the double-layered film consisting of a chiral layer and a fluorescent layer. More noticeably, for double-layered films, the sense of CPL signals can be switched by changing the direction of excitation light. This work opens up new strategies for exploring tunable multiple- and white-color CPL materials.

Region-related and layer-specific permeability of the iris vasculature with morphological mechanism: A novel understanding of blood-aqueous barrier.

The permeability of iris blood vessels has an important role in maintaining aqueous humor (AH) homeostasis, contributing to variation in iris volume and probably the pathogenesis of angle closure glaucoma. This study investigates the permeability of the iris microvasculature to plasma-derived protein and correspond it with the morphologic characteristics of vascular mural cells (MCs). Twenty-two enucleated porcine eyes were used in this study. 12 eyes were micro-perfused with vehicle alone as control or with FITC-albumin as a marker of protein leakage and histological sections subsequently made to examine for FITC-albumin presence. The other 10 eyes were immunolabeled via micro-perfusion for αSMA and VE-cadherin to investigate their topographic distribution in the porcine iris vasculature, and to cross correspond with the locations of FITC-albumin deposits. Distribution of FITC-signals exhibited a site-dependent pattern and time-dependent change in the iris. Fluorescence was initially detected around capillaries in the superficial and deep layer of the iris microvascular network. The pupillary region and the iris root retained more fluorescent signal than the iridal ciliary region. At low magnification, αSMA labelling displayed a regional variation which was inversely correlated with vascular permeability. At the cellular level, αSMA labeling corresponded with vascular MCs distribution in the iris vascular network. The correspondence between iris microvascular permeability to FITC-albumin and the pattern of αSMA distribution and MCs coverage adds to the understanding of the elements comprising the blood-aqueous barrier with implications for the bio-mechanics of iris volume change.

Influence of miosis and laser peripheral iridotomy on intraocular lens power calculation in patients with primary angle closure disease.

OBJECTIVES: To evaluate the effect of miosis and laser peripheral iridotomy (LPI) on intraocular lens (IOL) power prediction and ocular biometry in eyes with primary angle closure disease (PACD). METHODS: In this prospective observational study, primary angle closure suspects (PACS), and subjects classified with primary angle closure (PAC)/primary angle-closure glaucoma (PACG) undergoing LPI were enrolled. Ocular biometric parameters were measured with IOLMaster700 at baseline (T0), one week after pilocarpine instillation (T1), and another week post LPI (T2). Biometric changes and the IOL power predicted for emmetropia using Barrett Universal II, Haigis, Holladay2, Hoffer Q and SRK/T formulae were analysed and compared among different time points. RESULTS: 100 eyes of 50 PACS and 50 PAC/PACG patients were enrolled. Following pilocarpine-induced miosis, lens thickness (LT) increased and anterior chamber depth (ACD) decreased (all groups p < 0.01), while white-to-white diameter decreased and central corneal thickness increased significantly only in the PACS cohort (both p < 0.01). Compared to baseline, LPI induced an increase of ACD and a slight decrease of LT in PACS (both p < 0.01), whereas only axial length changed significantly (p = 0.012) in the PAC/PACG cohort. Regardless of the formula used, no significant difference to the predicted IOL power for emmetropia existed among the three time points in each group (all p > 0.1). CONCLUSION: We report the changes of anterior segment parameters induced by miosis and LPI in PACD. These interventions do not significantly affect the IOL power calculation predicted for emmetropia in Chinese eyes when common third-, fourth-and new generation IOL formulae are used.

Application of Precision-Cut Lung Slices as an In Vitro Model for Research of Inflammatory Respiratory Diseases.

The leading cause of many respiratory diseases is an ongoing and progressive inflammatory response. Traditionally, inflammatory lung diseases were studied primarily through animal models, cell cultures, and organoids. These technologies have certain limitations, despite their great contributions to the study of respiratory diseases. Precision-cut lung slices (PCLS) are thin, uniform tissue slices made from human or animal lung tissue and are widely used extensively both nationally and internationally as an in vitro organotypic model. Human lung slices bridge the gap between in vivo and in vitro models, and they can replicate the living lung environment well while preserving the lungs' basic structures, such as their primitive cells and trachea. However, there is no perfect model that can completely replace the structure of the human lung, and there is still a long way to go in the research of lung slice technology. This review details and analyzes the strengths and weaknesses of precision lung slices as an in vitro model for exploring respiratory diseases associated with inflammation, as well as recent advances in this field.

Optically active polymer particles with programmable surface microstructures constructed using chiral helical polyacetylene.

Micro/nanoparticles with surface microstructures have attracted tremendous attention due to their fascinating structures and properties. Herein, we present the first strategy for producing optically active polymer particles with varying surface microstructures via a template surface modification process in which achiral particles act as the template and helical substituted polyacetylene acts as the chiral component. To prepare the designed chiral-functionalized particles, template particles were first reacted with propargylamine to produce alkynylated template particles. The alkynylated templates further participated in the polymerization of chiral alkyne monomers through a surface grafting precipitation polymerization approach, resulting in achiral particles with surface microstructures covalently bonded with a chiral helical polymer. SEM images ascertain the production of chiral-functionalized particles showing various shapes (jar-like, golf ball-like, and raspberry-like particles). Furthermore, CD and UV-vis absorption spectra demonstrate that the grafted polyacetylene chains adopt a predominantly single-handed helical conformation, thereby affording composite particles with optical activity. Using the established protocol, numerous advanced chiral-functionalized micro/nanostructures are expected to be designed and constructed.

A systemic review and network meta-analysis of accuracy of intraocular lens power calculation formulas in primary angle-closure conditions.

BACKGROUND: For primary angle-closure and angle-closure glaucoma, the fact that refractive error sometimes deviates from predictions after intraocular lens (IOL) implantation is familiar to cataract surgeons. Since controversy remains in the accuracy of IOL power calculation formulas, both traditional and network meta-analysis on formula accuracy were conducted in patients with primary angle-closure conditions. METHODS: A comprehensive literature search was conducted through Aug 2022, focusing on studies on intraocular lens power calculation in primary angle-closure (PAC) and primary angle-closure glaucoma (PACG). A systemic review and network meta-analysis was performed. Quality of studies were assessed. Primary outcomes were the mean absolute errors (MAE) and the percentages of eyes with a prediction error within ±0.50 diopiters (D) or ±1.00 D (% ±0.50/1.00 D) by different formulas. RESULTS: Six retrospective studies involving 419 eyes and 8 formulas (Barrett Universal II, Kane, SRK/T, Hoffer Q, Haigis, Holladay I, RBF 3.0 and LSF) were included. SRK/T was used as a reference as it had been investigated in all the studies included. Direct comparison showed that none of the involved formula outperformed or was defeated by SRK/T significantly in terms of either MAE or % ±0.50/1.00 D (all P>0.05). Network comparison and ranking possibilities disclosed BUII, Kane, RBF 3.0 with statistically insignificant advantage. No significant publication bias was detected by network funnel plot. CONCLUSIONS: No absolute advantage was disclosed among the formulas involved in this study for PAC/PACG eyes. Further carefully designed studies are warranted to evaluate IOL calculation formulae in this target population. TRAIL REGISTRATION: Registration: PROSEPRO ID: CRD42022326541.

[Study on chemical constituents of Wedelia trilobata].

A new taraxer-based triterpenoid ester, taraxer-14-en-30-al-3ß-O-palmitate(1), was isolated from the whole plant of Wedelia trilobata, along with six known compounds, ent-kaur-16-en-19-oic acid(2), 16α-hydroxy-ent-kauran-19-oic acid(3), tara-xerol(4), ß-amyrin(5), 1ß-acetoxy-4α, 9α-dihydroxy-6ß-isobutyroxyprostatolide(6), and stigmasterol(7). Their structures were elucidated with use of a combination of spectroscopic techniques(IR, HR-ESI-MS, 1 D, 2 D NMR data) and chemical methods.

Glued diffraction optical elements with broadband and a large field of view.

High diffraction efficiency is an important requirement for hybrid diffractive-refractive optical systems with a wide field of view. The issue is that diffractive optical elements cannot maintain high diffraction efficiency across a designed waveband and range of incident angles simultaneously. Glued diffractive optical elements (GDOEs) consist of two single-layer diffractive elements, and optical adhesives are presented to address the problem. Two diffractive optical elements are glued together to reduce the straylight scattered into unwanted diffraction orders. The parameters of diffractive optical elements are optimized to achieve broadband high diffraction efficiency and modulation transfer function over a wide-incident-angle range. The GDOEs enable the system to realize a diffraction efficiency of over 90% when the incident angle is no more than 58°. Through gluing two single-layer diffractive optical elements together, we can minimize the inner reflection and refraction. Diffraction efficiency losses can be compensated by the optical adhesives layer, and image quality can be improved. Our design method could make possible the use of diffraction elements in different kinds of optical systems.

Synthesis of 1,2-Amino Alcohols by Photoredox-Mediated Decarboxylative Coupling of α-Amino Acids and DNA-Conjugated Carbonyls.

We report a DNA-compatible photoredox decarboxylative coupling of α-amino acids with carbonyl compounds to access DNA-encoded sp3-rich 1,2-amino alcohols. The reaction proceeds efficiently for a wide range of DNA-conjugated aldehydes and ketones and provides the desired 1,2-amino alcohols with conversions generally >50%. Additional utility of the developed protocol is demonstrated by one-pot cyclization of DNA-conjugated 1,2-amino alcohols into oxazolidiones and morpholinones. Lastly, qPCR and sequencing data analysis indicates no significant DNA damage upon photoredox decarboxylative coupling.

DNA-Compatible Copper-Catalyzed Oxidative Amidation of Aldehydes with Non-Nucleophilic Arylamines.

We report a DNA-compatible protocol for synthesizing amides from DNA-bound aldehydes and non-nucleophilic arylamines including aza-substituted anilines, 2-aminobenzimidazoles, and 3-aminopyrazoles. The reactions were carried out at room temperature and provided reasonable conversions and wide functional group compatibility. The reactions were also successful when employing aryl and aliphatic aldehydes. In addition, qPCR and NGS data suggested no negative impact on DNA integrity after the copper-mediated oxidative amidation reaction.